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A complex series of studies by Oelschlegel et al. in a murine model of cerebral malaria establishes a temporal sequence of events linking decreased venous efflux to impaired perfusion, edema, and neuroinflammation. The relevance to human cerebral malaria is discussed, including the heterogeneity recognized in recent investigations of cerebrovascular hemodynamics. [ABSTRACT FROM AUTHOR]

IntroductionTreatment of brain tumors in dogs can be associated with significant morbidity and reliable prognostic factors are lacking. Dynamic contrast-enhanced computed tomography (DCECT) can be used to assess tumor perfusion. The objectives of this study were to assess perfusion parameters and change in size of suspected brain tumors before and during radiotherapy (RT) depending on their location and find a potential correlation with survival.MethodsSeventeen client-owned dogs with suspected brain tumors were prospectively recruited. All dogs had a baseline DCECT to assess mass size, blood volume (BV), blood flow (BF), and transit time (TT). Twelve dogs had a repeat DCECT after 12 Gy of megavoltage RT. Survival times were calculated.ResultsIntra-axial masses had lower BF (p = 0.005) and BV (p

Background: Prediction of tumor shrinkage and pattern of treatment response following neoadjuvant endocrine therapy (NET) for estrogen receptor positive (ER+), Her2 negative (Her2–) breast cancers have had limited assessment. We examined if ultrasound (US) and Ki–67 could predict the pathologic response to treatment with NET and how the pattern of response may impact surgical planning. Methods: A total of 103 postmenopausal women with ER+, HER2– breast cancer enrolled on the FELINE trial had Ki–67 obtained at baseline, day 14, and surgical pathology. A total of 70 patients had an US at baseline and at the end of treatment (EOT). A total of 48 patients had residual tumor bed cellularity (RTBC) assessed. The US response was defined as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). CR or PR on imaging and ≤70% residual tumor bed cellularity (RTBC) defined a contracted response pattern. Results: A decrease in Ki–67 at day 14 was not predictive of EOT US response or RTBC. A contracted response pattern was identified in one patient with CR and in sixteen patients (33%) with PR on US. Although 26 patients (54%) had SD on imaging, 22 (85%) had RTBC ≤70%, suggesting a non-contracted response pattern of the tumor bed. The remaining four (15%) with SD and five with PD had no response. Conclusion: Ki–67 does not predict a change in tumor size or RTBC. NET does not uniformly result in a contracted response pattern of the tumor bed. Caution should be taken when using NET for the purpose of downstaging tumor size or converting borderline mastectomy/lumpectomy patients. [ABSTRACT FROM AUTHOR]

Background: It is thought that the susceptibility of chronic myeloid leukemic (CML) cells to imatinib (IM) is increased by high miR-153-3p expression. Aim: To establish the association of miR-153-3p expression with treatment response to IM in CML patients. Methods: Sixty CML patients were included and divided into two groups consistent with their response to treatment whether sensitive or resistant to IM. Ten healthy normal participants were enrolled as control group. RNA was extracted from serum to work out miR-153-3p expression utilizing real-time quantitative reverse transcription polymerase chain reaction. The primers were supplied by Macrogen Inc. Results: 27 patients were sensitive to imatinib and 33 were resistant to imatinib. The ratio of male to female was 1.14:1. The bulk (58%) of patients were within the age range of 41-60 years. Weight and gender did not significantly differ between the two patient groups. The mean patients' CT of miR-153-3p was significantly above the control group and the sensitive group. The mean DCT value in resistant group was significantly above that of the sensitive group while insignificantly above that of the control group. The mean DDCT in resistant group was significantly higher than that of the sensitive group. The miR-153-3p expression showed significantly lower fold change than the sensitive group. Conclusion: There is miR-153-3p expression downregulation in resistant CML patients indicating unresponsiveness to treatment with imatinib. [ABSTRACT FROM AUTHOR]

Introduction: Renal carcinoma accounts for approximately 2% of cancer disorders globally, with a higher incidence in North America and Northern Europe. In Mexico, this pathology represents the fourteenth cause of death. About 19,000 new cases are diagnosed each year. This study compared the response to molecular target therapy in patients with recurrence of clear cell renal cancer after radical nephrectomy vs. patients with an initial diagnosis of metastatic clear cell renal cancer in HEP. Material and methods: This study was a comparative, impact, scrutiny, cross-sectional, homodemic, single-center study with prospective directionality. Data analysis was performed using descriptive statistics, measures of central tendency, and dispersion. To test the hypothesis, Student's t-test, U Mann-Whitney, X2 will be used. Results: Sixty participants were included, 43 (71.7%) were men and 17 (28.7%) were women. The mean age was 59.63 years, p = 0.357. A disease response to treatment was observed, stable in 23 patients (38.3%), partial in 14 patients (23.3%), complete in 11 patients (18.3%), and disease progression in 12 patients (20%). This response to treatment was evaluated by comparing both groups, obtaining a p = 0.963. Discussion: No difference was observed in the response to treatment with molecular target therapy at one year of follow-up, between group 1 and group 2 (p = 0.963), patients with kidney cancer who present with the disease, when compared with those who recur later. to radical nephrectomy, at 12 months of follow-up, they present a similar response, regardless of the TMN, the nuclear grade of the tumor (p = 0.156), or the type of medication used (p = 0.653). Conclusions: In kidney cancer, surgical treatment is the only curative option in localized disease. Once metastatic disease occurs, regardless of whether it is after curative treatment, or as a debut at the diagnosis of this cancer, the response to treatment with molecular target therapy will be similar. It is necessary to perform more studies of this type, a greater number of patients, a longer follow-up time, as well as a greater number of hospital centers so that the results obtained in this research are validated and applied to the population in general. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) is part of the standard treatment of breast cancer (BC) because of its effects on relapse reduction and survival. However, response to treatment is highly variable, and some patients may develop disease progression (DP), a second primary cancer, or may succumb to the disease. Antioxidant systems and inflammatory processes are associated with the onset and development of BC and play a role in resistance to treatment. Here, we report our investigation into the clinical evolution of BC patients, and the impact of RT on the circulating levels of the antioxidant enzyme paraoxonase-1 (PON1), cytokines, and other standard biochemical and hematological variables. Gradient Boosting Machine (GBM) algorithm was used to identify predictive variables. This was a retrospective study in 237 patients with BC. Blood samples were obtained pre- and post-RT, with samples of healthy women used as control subjects. Results showed that 24 patients had DP eight years post-RT, and eight patients developed a second primary tumor. The algorithm identified interleukin-4 and total lymphocyte counts as the most relevant indices discriminating between BC patients and control subjects, while neutrophils, total leukocytes, eosinophils, very low-density lipoprotein cholesterol, and PON1 activity were potential predictors of fatal outcome. [ABSTRACT FROM AUTHOR]

Baseline severity of alcohol use disorder (AUD) is an influencing factor in the response to medications recommended for the treatment of AUD. The scarce efficacy of AUD medications partly justifies their limited uses. We were interested in evaluating the efficacy of approved and recommended AUD medications using generic inverse-variance, an analysis facilitating comparison between medications and placebo both at the end of the study and, concomitantly, to baseline values for the same participants. We conducted a systematic review to include randomized controlled trials (RCTs) comparing any medication to placebo providing, both at baseline and end of treatment, percent heavy drinking days (%HDD), percent drinking days (%DD), and/or drinks per drinking day (DDD). We searched PubMed, Embase, PMC, and three CT registers from inception to April 2023. A total of 79 RCTs (11,737 AUD participants; 30 different medications) were included: 47 RCTs (8465 participants) used AUD medications, and 32 RCTs (3272 participants) used other medications. At baseline, participants consumed on average approximately 12 DDD, and experienced 70 % DD, and 61 % HDD. Placebo halved or reduced these values to a third. Compared to placebo, AUD medications further reduced these outcomes (moderate to high certainty evidence). Other medications reduced the DDD without modifying other alcohol outcomes. AUD medications increased the risk of developing adverse events (high-certainty evidence). Despite the large placebo effects, our results support the benefits of providing AUD medications to people with AUD, helping them reduce alcohol consumption. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction. Cancer mortality in diabetic patients has been reported to increase moderately compared to non-diabetic patients. The aim of the study aimed to assess the findings and identify radiotherapy's role in the comprehensive care of diabetic IBC patients with various hyperglycemia correction strategies. Methods. Patients with diabetes have shown a higher risk of radiation-induced cancer progression for tumor tissue, especially for inflammatory form. For 7 patients, to continue systematic chemotherapy with a scheme change (consecutive anthracyclines-taxanes, 2-week interval) and insulin with individual scheme for hyperglycemia correction on the basis of glycemic control – 1st group, the other (7 patients) – 2nd group, was given radiotherapy to the breast gland and lymphatic drainage ways. 45–50 Grey was prescribed for 25-28 fractions (per 1.8-2.0 Grey), 46–50 Grey in 23-25 fractions were used for zones of regional metastasis and for hyperglycemia correction metformin 2000 mg/day PO divided q8-12hr with meal on the basis of glycemic control. Results. Assessed were the number of patients who qualified for surgery and overall survival for 24 months. 2nd group showed a superior response following resistance to prior systemic treatment. Thus, 5 (71.41%) of the 7 patients exhibited a consistent response – complete or partial regression. There were only 2 individuals (28.61%) who responded to treatment among the patients who maintained chemotherapy. Conclusions. Breast cancer of the aggressive IBC variety requires multidisciplinary treatment from breast surgery, medical, and radiation oncology. Patients with diabetes appear to experience more side effects from radiation therapy than patients without the disease. Hyperglycemia, higher total RT doses, and radiosensitizers are a few techniques that can improve the impact of RT on local-regional management. Local-regional control rates for IBC are increasing with an individual patient strategy. Metformin also improves insulin resistance and has anticancer benefits. [ABSTRACT FROM AUTHOR]

Aim: To investigate the utility of systemic immune-inflammation index (SII) in predicting response to cardiac resynchronization therapy (CRT) among patients with heart failure (HF). Method: A total of 78 patients with HF who underwent CRT device implantation were included in this 6-month follow up study. Data on laboratory findings including complete blood count, blood biochemistry and SII as well as the transthoracic echocardiography findings were recorded at baseline prior to CRT device implantation and 6 months after CRT. Results: The criteria for response to CRT including improvements in New York Heart Association (NYHA), left ventricular end-systolic volume (LVESV) (decreased by =15%) and ejection fraction (EF) (increased by=10%) were met by 73.1%, 65.4% and 69.2% of patients, respectively. In patients with decreased vs. increased SII values during 6-month therapy, the likelihood of meeting LVESV (84.3 vs. 15.7%, p<0.001), EF (81.5 vs. 18.5%, p<0.001) and NYHA (77.2 vs. 22.8%, p<0.001) response criteria for successful CRT were significantly higher. Multivariate analysis revealed that decrease in SII (OR 0.982, 95% CI: 0.970 to 0.995, p=0.006) and TAPSE (OR 0.602, 95% CI. 0.396 to 0.916, p=0.018) during treatment as the only significant determinants of presence of response to CRT in heart failure (HF) patients. Conclusions: Our findings seem to indicate the favorable utility of SII, as a non-invasive readily available marker, in predicting response to CRT and thus enabling a beneficial reverse remodeling process via timely implementation of advanced treatments in HF patients. [ABSTRACT FROM AUTHOR]

The treatment of head and neck and salivary gland tumours is complicated and evolves constantly. Prognostic and predictive indicators of response to treatment are enormously valuable for designing individualized therapies, which justifies their research and validation. Some biomarkers, such as p16, Epstein–Barr virus, PD-L1, androgen receptors and HER-2, are already used routinely in clinical practice. These biomarkers, along with other markers that are currently under development, and the massively parallel sequencing of genes, ensure future advances in the treatment of these neoplasms. In this consensus, a group of experts in the diagnosis and treatment of tumours of the head and neck and salivary glands were selected by the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica—SEAP) and the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica—SEOM) to evaluate the currently available information and propose a series of recommendations to optimize the determination and daily clinical use of biomarkers. [ABSTRACT FROM AUTHOR]

Background: An interplay between immune cells and resident skin and joint stromal cells is implicated in psoriatic arthritis (PsA), yet the mechanisms remain elusive with a paucity of molecular biomarkers for activity and response. Combined transcriptomic and immunophenotypic analysis of whole blood and skin fibroblasts could provide further insights. Methods: Whole blood RNA-seq was performed longitudinally in 30 subjects with PsA at the beginning, one and six months after treatment, with response defined at six months. As control groups, 10 healthy individuals and 10 subjects with rheumatoid arthritis (RA) were recruited combined with public datasets from patients with psoriasis (PsO) and systemic lupus erythematous (SLE). Differential expression analysis and weighted gene co-expression network analysis were performed to identify gene expression signatures, while deconvolution and flow cytometry to characterize the peripheral blood immune cell profile. In a subset of affected and healthy individuals, RNA-seq of skin fibroblasts was performed and subjected to CellChat analysis to identify the blood-skin fibroblast interaction network. Results: PsA demonstrated a distinct "activity" gene signature in the peripheral blood dominated by TNF- and IFN-driven inflammation, deregulated cholesterol and fatty acid metabolism and expansion of pro-inflammatory non-classical monocytes. Comparison with the blood transcriptome of RA, PsO, and SLE revealed a "PsA-specific signature" enriched in extracellular matrix remodeling. This was further supported by the skin fibroblast gene expression profile, displaying an activated, proliferating phenotype, and by skin-blood interactome analysis revealing interactions with circulating immune cells through WNT, PDGF and immune-related semaphorins. Of note, resistance to treatment was associated with upregulation of genes involved in TGFβ signaling and angiogenesis and persistent increase of nonclassical monocytes. Differentially expressed genes related to platelet activation and hippo signaling discriminated responders and non-responders as early as one month after treatment initiation. Conclusion: Transcriptome analysis of peripheral blood and skin fibroblasts in PsA reveals a distinct disease activity signature and supports the involvement of skin fibroblasts through their activation and interaction with circulating immune cells. Aberrant TGFβ signaling and persistently increased nonclassical monocytes characterize treatment-resistant PsA, with proinflammatory pathways related to platelet activation and Hippo signaling predicting early response to treatment. [ABSTRACT FROM AUTHOR]

Introduction Alopecia areata (AA) is a common, chronic inflammatory, non-scarring form of hair loss affecting 0.1-0.2% of the population. It is a psychosomatic disease involving a T-cell-mediated immune reaction against hair follicle antigens during the anagen phase. Psychiatric morbidity in dermatological patients can significantly affect their quality of life and disease progression. Identifying and addressing these comorbidities in AA patients is crucial. Aim This study aimed to estimate the prevalence of depression and its associated factors among patients diagnosed with alopecia areata (AA). Methods The present study is a cross-sectional, descriptive, and analytical study conducted at Farhat Hached Hospital in Sousse, Tunisia, during the period from August to December 2019. Participants were recruited from the Dermatology Outpatient Department. The questionnaire covered socio-demographic characteristics, personal and family history, AA history, clinical presentation, disease severity (SALT score), nail involvement, and depression assessment using the Hamilton Depression Scale (validated Arabic version). Results A total of 60 AA patients were enrolled, with a mean age of 37.6 ± 12.9 years. Females exhibited a predominant representation, with a male to female ratio (M/F) of 0.76. According to the Hamilton Depression Scale (HAM-D), 31 cases (51.7%) were depressed, with a mean depression scale score of 11.33 (±6.57 SD). The presence of depression was significantly associated with younger age (p=0.018), the presence of the eyelashes/eyebrows form (p=0.035), nail involvement (p= 0.03), and a poor response to treatment (p=0.004). Conclusion Our research highlights the importance of providing psychological support to alopecia areata patients.

In this review article four clinical comparative studies in axial spondylarthritis (axSpA) are presented and discussed. SURPASS as the only head-to-head study investigated the effect of adalimumab biosimilar disease-modifying antirheumatic drug (bsDMARD) or secukinumab on radiographic progression over a time period of 2 years. Overall, the radiographic progression of the spine was low and no significant difference between adalimumab bsDMARD or secukinumab was noted. The three other studies were not constructed as direct head-to-head studies but compared the efficacy of non-steroidal antirheumatic drugs (NSARD) with and without simultaneous treatment with biological DMARDs (bDMARD). The CONSUL study showed no statistically significant difference in the delay of radiographic progression of the spine over 2 years in radiographic axSpA (r-axSpA) patients, who underwent either combined treatment with golimumab and celecoxib or treatment with golimumab alone over 2 years. The ESTHER study showed that patients with early axSpA active inflammatory lesions, which were detected by whole-body magnetic resonance imaging (MRI), showed a significantly greater improvement under treatment with etanercept than those treated with sulfasalazine. The INFAST study showed that patients with early active axSpA who received a combined treatment of infliximab and naproxen, achieved a clinical remission twice as frequently as those who only received naproxen. Therefore, for the endpoint of radiological progression no difference could be shown in the inhibition of radiological progression between the mechanisms of action investigated. The comparative data for the endpoint of clinical efficacy showed that patients with bDMARDs showed a clearly better response to treatment than patients with NSAR or conventional synthetic DMARDs (csDMARD)., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Severe acute malnutrition (SAM) can be diagnosed using weight-for-height Z-score (WHZ) and/or mid-upper arm circumference (MUAC). Although some favor using MUAC alone, valuing its presumed ability to identify children at greatest need for nutritional care, the functional severity and physiological responses to treatment in children with varying deficits in WHZ and MUAC remain inadequately characterized., Objective: We aimed to compare clinical and biochemical responses to treatment in children with 1) both low MUAC and low WHZ, 2) low MUAC-only, and 3) low WHZ-only., Methods: A multicenter, observational cohort study was conducted in children aged 6-59 mo with nonedematous, uncomplicated SAM in Bangladesh, Burkina Faso, and Liberia. Anthropometric measurements and critical indicators were collected 3 times during treatment; metrics included clinical status, nutritional status, viability, and serum leptin, a biomarker of mortality risk in SAM., Results: Children with combined MUAC and WHZ deficits had greater increases in leptin levels during treatment than those with low MUAC alone, showing a 34.4% greater increase on the second visit (95% confidence interval [CI]: 7.6%, 43.6%; P = 0.02) and a 34.3% greater increase on the third visit (95% CI: 13.2%, 50.3%; P = 0.01). Similarly, weight gain velocity was higher by 1.56 g/kg/d in the combined deficit group (95% CI: 0.38, 2.75; P = 0.03) compared with children with low MUAC-only. Children with combined deficits had higher rates of iron deficiency and wasting while those with low WHZ alone and combined deficits had higher rates of tachypnea and pneumonia during treatment., Conclusions: Given the comparable treatment responses of children with low WHZ alone and those with low MUAC alone, and the greater vulnerability at admission and during treatment in those with combined deficits, our findings support retaining WHZ as an independent diagnostic and admission criterion of SAM, alongside MUAC. This trial was registered at www., Clinicaltrials: gov/study/NCT03400930 as NCT03400930., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

The purpose is to present a modern data on the possibilities of positron emission computed tomography combined with computed tomography (PET/CT) in the diagnosis, staging and monitoring of prostate cancer (PC).Material and Methods. A search and analysis of the largest domestic and English-language databases (Elibrary, PubMed, Elsevier, etc.) on this problem was carried out. 37 sources were found devoted to studying the results of clinical trials of the diagnostic capabilities of PET/CT with various radiopharmaceuticals.Results. The presented data on the possibilities of PET/CT with various radiopharmaceuticals in the diagnosis of primary prostate cancer, imaging of lymphogenous and distant metastases, as well as in assessing the effectiveness of treatment.Conclusion. This review of the literature showed that the use of PET/CT in prostate cancer largely depends on the chosen radiopharmaceutical. Moreover, it is PET/CT with PSMA-based radiopharmaceuticals that is the most promising method for examining patients with prostate cancer and can be recommended as an additional study in cases where other methods of radiation diagnostics do not give an unambiguous answer. The development of new and improving the already used radiopharmaceuticals, which will increase the sensitivity, specificity and accuracy of the diagnosis, staging, monitoring and prognosis of treatment of prostate cancer, remains relevant.

BackgroundAn interplay between immune cells and resident skin and joint stromal cells is implicated in psoriatic arthritis (PsA), yet the mechanisms remain elusive with a paucity of molecular biomarkers for activity and response. Combined transcriptomic and immunophenotypic analysis of whole blood and skin fibroblasts could provide further insights.MethodsWhole blood RNA-seq was performed longitudinally in 30 subjects with PsA at the beginning, one and six months after treatment, with response defined at six months. As control groups, 10 healthy individuals and 10 subjects with rheumatoid arthritis (RA) were recruited combined with public datasets from patients with psoriasis (PsO) and systemic lupus erythematous (SLE). Differential expression analysis and weighted gene co-expression network analysis were performed to identify gene expression signatures, while deconvolution and flow cytometry to characterize the peripheral blood immune cell profile. In a subset of affected and healthy individuals, RNA-seq of skin fibroblasts was performed and subjected to CellChat analysis to identify the blood-skin fibroblast interaction network.ResultsPsA demonstrated a distinct “activity” gene signature in the peripheral blood dominated by TNF- and IFN-driven inflammation, deregulated cholesterol and fatty acid metabolism and expansion of pro-inflammatory non-classical monocytes. Comparison with the blood transcriptome of RA, PsO, and SLE revealed a “PsA-specific signature” enriched in extracellular matrix remodeling. This was further supported by the skin fibroblast gene expression profile, displaying an activated, proliferating phenotype, and by skin-blood interactome analysis revealing interactions with circulating immune cells through WNT, PDGF and immune-related semaphorins. Of note, resistance to treatment was associated with upregulation of genes involved in TGFβ signaling and angiogenesis and persistent increase of non-classical monocytes. Differentially expressed genes related to platelet activation and hippo signaling discriminated responders and non-responders as early as one month after treatment initiation.ConclusionTranscriptome analysis of peripheral blood and skin fibroblasts in PsA reveals a distinct disease activity signature and supports the involvement of skin fibroblasts through their activation and interaction with circulating immune cells. Aberrant TGFβ signaling and persistently increased non-classical monocytes characterize treatment-resistant PsA, with pro-inflammatory pathways related to platelet activation and Hippo signaling predicting early response to treatment.

This work aims to summarize predictive biomarkers to guide treatment choice in DME. Intravitreal anti-VEGF is considered the gold standard treatment for centers involving DME, while intravitreal steroid treatment has been established as a second-line treatment in DME. However, more than 1/3 of the patients do not adequately respond to anti-VEGF treatment despite up to 4-weekly injections. Not surprisingly, insufficient response to anti-VEGF therapy has been linked to low-normal VEGF levels in the serum and aqueous humor. These patients may well benefit from an early switch to intravitreal steroid treatment. In these patients, morphological biomarkers visible in OCT may predict treatment response and guide treatment decisions. Namely, the presence of a large amount of retinal and choroidal hyperreflective foci, disruption of the outer retinal layers and other signs of chronicity such as intraretinal cysts extending into the outer retina and a lower choroidal vascular index are all signs suggestive of a favorable treatment response of steroids compared to anti-VEGF. This paper summarizes predictive biomarkers in DME in order to assist individual treatment decisions in DME. These markers will help to identify DME patients who may benefit from primary dexamethasone treatment or an early switch. [ABSTRACT FROM AUTHOR]

Leishmaniasis is caused by protozoans of the Leishmania genus, which includes more than 20 species capable of infecting humans worldwide. In the Americas, the most widespread specie is L. braziliensis, present in 18 countries including Bolivia. The taxonomic position of the L. braziliensis complex has been a subject of controversy, complicated further by the recent identification of a particular subpopulation named L. braziliensis atypical or outlier. The aim of this study was to carry out a systematic analysis of the L. braziliensis complex in Bolivia and to describe the associated clinical characteristics. Forty‐one strains were analyzed by sequencing an amplified 1245 bp fragment of the hsp70 gene, which allowed its identification as: 24 (59%) L. braziliensis, 16 (39%) L. braziliensis outlier, and one (2%) L. peruviana. In a dendrogram constructed, L. braziliensis and L. peruviana are grouped in the same cluster, whilst L. braziliensis outlier appears in a separate branch. Sequence alignment allowed the identification of five non‐polymorphic nucleotide positions (288, 297, 642, 993, and 1213) that discriminate L. braziliensis and L. peruviana from L. braziliensis outlier. Moreover, nucleotide positions 51 and 561 enable L. peruviana to be discriminated from the other two taxa. A greater diversity was observed in L. braziliensis outlier than in L. braziliensis‐L. peruviana. The 41 strains came from 32 patients with tegumentary leishmaniasis, among which 22 patients (69%) presented cutaneous lesions (11 caused by L. braziliensis and 11 by L. braziliensis outlier) and 10 patients (31%) mucocutaneous lesions (eight caused by L. braziliensis, one by L. braziliensis outlier, and one by L. peruviana). Nine patients (28%) simultaneously provided two isolates, each from a separate lesion, and in each case the same genotype was identified in both. Treatment failure was observed in six patients infected with L. braziliensis and one patient with L. peruviana. [ABSTRACT FROM AUTHOR]

Simple Summary: High tumor-infiltrating lymphocyte (TIL) levels are associated with an increased response to neoadjuvant chemotherapy (NAC) in breast cancer (BC). The seasonal fluctuation of TILs in breast cancer is poorly documented. In this study, we compared pre- and post-treatment immune infiltration, the treatment response as assessed by means of pathological complete response (pCR) rates, and survival according to the seasonality of BC diagnoses in a clinical cohort of patients treated with NAC. We found no association between seasonality and baseline TIL levels or pCR rates. We found that post-NAC stromal lymphocyte infiltration was lower when cancer was diagnosed in the summer, especially in the subgroup of patients with TNBC. Our data do not support the hypothesis that the seasonality of diagnoses has a major impact on the natural history of BC treated with NAC. Breast cancer (BC) is the most common cancer in women worldwide. Neoadjuvant chemotherapy (NAC) makes it possible to monitor in vivo response to treatment. Several studies have investigated the impact of the seasons on the incidence and detection of BC, on tumor composition, and on the prognosis of BC. However, no evidence is available on their association with immune infiltration and the response to treatment. The objective of this study was to analyze pre- and post-NAC immune infiltration as assessed by TIL levels, the response to treatment as assessed by pathological complete response (pCR) rates, and oncological outcomes as assessed by relapse-free survival (RFS) or overall survival (OS) according to the seasonality of BC diagnoses in a clinical cohort of patients treated with neoadjuvant chemotherapy. Out of 1199 patients, the repartition of the season at BC diagnosis showed that 27.2% were diagnosed in fall, 25.4% in winter, 24% in spring, and 23.4% in summer. Baseline patient and tumor characteristics, including notable pre-NAC TIL levels, were not significantly different in terms of the season of BC diagnosis. Similarly, the pCR rates were not different. No association for oncological outcome was identified. Our data do not support the idea that the seasonality of diagnoses has a major impact on the natural history of BC treated with NAC. [ABSTRACT FROM AUTHOR]

Aim: To test radiomic approach in patients with metastatic neuroendocrine tumors (NETs) treated with Everolimus, with the aim to predict progression-free survival (PFS) and death. Materials and methods: Twenty-five patients with metastatic neuroendocrine tumors, 15/25 pancreatic (60%), 9/25 ileal (36%), 1/25 lung (4%), were retrospectively enrolled between August 2013 and December 2020. All patients underwent contrast-enhanced CT before starting Everolimus, histological diagnosis, tumor grading, PFS, overall survival (OS), death, and clinical data collected. Population was divided into two groups: responders (PFS ≤ 11 months) and non-responders (PFS > 11 months). 3D segmentation was performed on whole liver of naïve CT scans in arterial and venous phases, using a dedicated software (3DSlicer v4.10.2). A total of 107 radiomic features were extracted and compared between two groups (T test or Mann–Whitney), radiomics performance assessed with receiver operating characteristic curve, Kaplan–Meyer curves used for survival analysis, univariate and multivariate logistic regression performed to predict death, and interobserver variability assessed. All significant radiomic comparisons were validated by using a synthetic external cohort. P < 0.05 is considered significant. Results: 15/25 patients were classified as responders (median PFS 25 months and OS 29 months) and 10/25 as non-responders (median PFS 4.5 months and OS 23 months). Among radiomic parameters, Correlation and Imc1 showed significant differences between two groups (P < 0.05) with the best performance (internal cohort AUC 0.86–0.84, P < 0.0001; external cohort AUC 0.84–0.90; P < 0.0001). Correlation < 0.21 resulted correlated with death at Kaplan–Meyer analysis (P = 0.02). Univariate analysis showed three radiomic features independently correlated with death, and in multivariate analysis radiomic model showed good performance with AUC 0.87, sensitivity 100%, and specificity 66.7%. Three features achieved 0.77 ≤ ICC < 0.83 and one ICC = 0.92. Conclusions: In patients affected by metastatic NETs eligible for Everolimus treatment, radiomics could be used as imaging biomarker able to predict PFS and death. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is becoming the predominant liver disease worldwide, and vitamin E has been clinically shown to improve histological parameters in a subset of patients. In this narrative review, we investigate whether genetic factors may help to explain why some patients show histological improvements upon high-dose alpha-tocopherol (αT) treatment while others do not. In summary, we identified two factors that are associated with treatment response, including genetic variations in haptoglobin as well as fatty acid desaturase 1/2 (FADS1/FADS2). Other genetic variants such as in alpha-tocopherol transfer protein (αTTP), tocopherol associated protein (TAP), transmembrane 6 superfamily 2 (TM6SF2), cluster of differentiation 36 (CD36), and proteins involved in lipoprotein metabolism may also play a role, but have not yet been investigated in a clinical context. We propose to further validate these associations in larger populations, to then use them as a clinical tool to identify the subset of patients that will benefit the most from vitamin E supplementation. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study is to evaluate uterine artery embolization (UAE) for the management of symptomatic uterine leiomyomas regarding changes in quality of life after treatment in a large patient collective. This study retrospectively analyzed prospectively acquired standardized questionnaires of patients treated with UAE. Clinical success was evaluated before and after embolization. Patients were stratified into short- (≤ 7 months) and long-term (> 7 months) follow-up groups depending on the time of completion of the post-interventional questionnaire. Uterine leiomyomas were furthermore divided into small (< 10 cm) and large (≥ 10 cm) tumors based on the diameter of the dominant fibroid. Results: A total of 245 patients were included into the final data analysis. The Kaplan–Meier analysis showed a cumulative clinical success rate of 75.8% after 70 months until the end of follow-up (9.9 years). All questionnaire subscales showed a highly significant clinical improvement from baseline to short- and long-term follow-up (p < 0.001). Patients with small fibroids showed a significantly better response to UAE in multiple subcategories of the questionnaire than patients with fibroids ≥ 10 cm who had a twofold higher probability of re-intervention in the Cox-regression model. Conclusions: UAE is an effective treatment method for symptomatic fibroids that leads to quick relief of fibroid-related symptoms with marked improvement of quality of life and is associated with a low risk for re-interventions. Patients with small fibroids tend to show a better response to UAE compared to patients with large fibroids. Trial registration Charité institutional review board, EA4/167/20. Registered 27 November 2020—Retrospectively registered. https://ethikkommission.charite.de/ [ABSTRACT FROM AUTHOR]

Evidence-based, early intervention significantly improves developmental outcome in young children with autism. Nonetheless, there is high interindividual heterogeneity in developmental trajectories during the therapy. It is established that starting intervention as early as possible results in better developmental outcomes. But except for younger age at start, there is no clear consensus about behavioral characteristics that could provide a reliable individual prediction of a child's developmental outcome after receiving an early intervention. In this study, we analyze developmental trajectories of preschoolers with autism who received 2 years of intervention using the Early Start Denver Model (ESDM) approach in Geneva, Switzerland in an individual setting (n = 55, aged 28.7 ± 5.1 months with a range of 15-42). Our aim was to identify early predictors of response to intervention. We applied a cluster analysis to distinguish between 3 groups based on their cognitive level at intake, and rates of cognitive change over the course of intervention. The first group of children only had a mild cognitive delay at intake and nearly no cognitive delay by the end of intervention (Higher Cognitive at baseline: HC). The children in the two other groups all presented with severe cognitive delay at baseline. However, they had two very different patterns of response to intervention. The majority significantly improved developmental scores over the course of intervention (Optimal Responders: OptR) whereas a minority of children showed only modest improvement (Minimal Responders: MinR). Further analyses showed that children who ended up having an optimal 2-year intervention outcome (OptR) were characterized by higher adaptive functioning at baseline combined with rapid developmental improvement during the first 6 months of intervention. Inversely, less significant progress by the sixth month of intervention was associated with a less optimal response to treatment (MinR). [ABSTRACT FROM AUTHOR]

Thyroid remnant after thyroidectomy is a major predictor for future recurrence of thyroid cancers; for which assessment, the accuracy of imaging is not optimal. To evaluate the value of the technetium uptake in the neck compared with neck ultrasonography, this application is used to predict future recurrence of differentiated thyroid cancer (DTC). The neck technetium uptake (NTU) value was acquired 20 min after injection of 1 mCi technetium by a camera. Patients were scheduled for forthcoming iodine ablation. Baseline risk factors were collected. Patients were followed for 10.5 (7 to 12) months when the records of the whole body scan, thyroglobulin, anti-thyroglobulin, neck ultrasonography, and the history of repeated iodine and surgical treatments were collected. The correlation of NTU and recurrence were studied. Out of 73 participants, 63 patients completed the study with established recurrence status and a valid NTU assessment. Baseline lymph node invasion (34.6% vs 80.0%; all 41.9%), extra-thyroid extension (17.0% vs 50.0%; all 22.2%), and tumor size (2.3 ± 2.1 vs 5.2 ± 2.4; all 2.7 ± 2.4) were higher in patients with future recurrence. But the NTU was similar in subjects with and without recurrence (−0.2 ± 0.7 vs 1.7 ± 6.3; all 59 ± 5.3). NTU was significantly lower in subjects with surgeries more extensive than thyroidectomy (P = 0.03). Recurrence cannot be predicted by NTU, but NTU may be used as a surrogate factor to determine the extent and completeness of the thyroidectomy surgery. [ABSTRACT FROM AUTHOR]

Evidence-based, early intervention significantly improves developmental outcome in young children with autism. Nonetheless, there is high interindividual heterogeneity in developmental trajectories during the therapy. It is established that starting intervention as early as possible results in better developmental outcomes. But except for younger age at start, there is no clear consensus about behavioral characteristics that could provide a reliable individual prediction of a child's developmental outcome after receiving an early intervention. In this study, we analyze developmental trajectories of preschoolers with autism who received 2 years of intervention using the Early Start Denver Model (ESDM) approach in Geneva, Switzerland in an individual setting (n = 55, aged 28.7 ± 5.1 months with a range of 15–42). Our aim was to identify early predictors of response to intervention. We applied a cluster analysis to distinguish between 3 groups based on their cognitive level at intake, and rates of cognitive change over the course of intervention. The first group of children only had a mild cognitive delay at intake and nearly no cognitive delay by the end of intervention (Higher Cognitive at baseline: HC). The children in the two other groups all presented with severe cognitive delay at baseline. However, they had two very different patterns of response to intervention. The majority significantly improved developmental scores over the course of intervention (Optimal Responders: OptR) whereas a minority of children showed only modest improvement (Minimal Responders: MinR). Further analyses showed that children who ended up having an optimal 2-year intervention outcome (OptR) were characterized by higher adaptive functioning at baseline combined with rapid developmental improvement during the first 6 months of intervention. Inversely, less significant progress by the sixth month of intervention was associated with a less optimal response to treatment (MinR).

Background. Despite ongoing treatment advancements in chronic heart failure (HF), mortality and readmission rates remain high for patients hospitalized for decompensated acute HF. These patients represent a distinct HF group, which requires emergent echocardiographic evaluation in an attempt to provide optimal and individualized acute care. The role of serial advanced echocardiographic assessment in acute HF for risk stratification and treatment guidance has not been thoroughly explored. Methods. The “Beyond Myo-HF Study” is a prospective, non-interventional cohort trial designed to enroll acutely admitted patients with symptoms and/or signs of HF. The aim of this study is to investigate whether intrahospital changes of conventional and novel echocardiographic indices of myocardial function and congestion-related markers can predict early mortality, late mortality, and HF rehospitalization. As per the protocol, all patients undergo a pair of state-of-the-art echocardiographic assessments, with a rigorous protocol including speckle tracking analysis of all cardiac chambers and myocardial work analysis for the left and right ventricle, upon admission and pre-discharge. Their laboratory profile is captured at those two time-points, and their therapeutic management is recorded. Patients will be followed-up for a median period of 12 months after enrollment. Conclusions. The “Beyond Myo-HF” study is an ongoing, prospective trial aspiring to provide deep insight into the pathophysiology of acute HF, to enlighten the reverse cardiac functional and anatomical remodeling during hospitalization, and to recognize echocardiographic patterns capable of predicting adverse outcomes during and post decompensation of acute HF.

Different therapeutic modalities for ano‐genital warts (AGWs) are available but data on the efficacy of 5‐fluorouracil 0.5%/salicylic acid 10% solution (5FU/SAsol) in the treatment of AGWs are scarse. We enrolled 17 patients with AGWs (14 males, 3 females with a mean age of 34.2 years) who gave written informed consent to the off‐label use of topical 5FU/Sasol. Response to treatment was assessed based on the AGWs number: complete if there was complete clearance of the lesions; partial if there was >50% decrease in the lesion number and none if there was <50% decrease in the lesion number. Considering together partial and complete treatment response, 88% of the patients at 3 months and 94% at 6 months benefited from the 5FU/SAsol treatment. 5FU/SAsol was well tolerated by all the patients except one who experienced a burning sensation immediately after the application. The clearance rate that we found for 5‐FU/SAsol after 3 months of treatment is comparable with that of the other commonly used therapeutic modalities (liquid nitrogen cryotherapy, imiquimod 5% cream). However, several patients on imiquimod and almost who underwent cryotherapy reported pain as adverse event while a mild pain was rarely reported with 5‐FU/Sasol. In conclusion, although nowadays in Italy 5‐FU/SAsol is marketed only for the treatment of actinic keratosis, our study described its effectiveness and tolerability also in the treatment of AGWs. Our data suggest that 5‐FU/SAsol should be considered not only in case of resistant/recurrent AGWs but also as the first therapeutic option, especially when the number of lesions is small. [ABSTRACT FROM AUTHOR]

A major challenge in the clinical management of patients with mesial temporal lobe epilepsy (MTLE) is identifying those who do not respond to antiseizure medication (ASM), allowing for the timely pursuit of alternative treatments such as epilepsy surgery. Here, we investigated changes in plasma metabolites as biomarkers of disease in patients with MTLE. Furthermore, we used the metabolomics data to gain insights into the mechanisms underlying MTLE and response to ASM. We performed an untargeted metabolomic method using magnetic resonance spectroscopy and multi- and univariate statistical analyses to compare data obtained from plasma samples of 28 patients with MTLE compared to 28 controls. The patients were further divided according to response to ASM for a supplementary and preliminary comparison: 20 patients were refractory to treatment, and eight were responsive to ASM. We only included patients using carbamazepine in combination with clobazam. We analyzed the group of patients and controls and found that the profiles of glucose (p = 0.01), saturated lipids (p = 0.0002), isoleucine (p = 0.0001), β-hydroxybutyrate (p = 0.0003), and proline (p = 0.02) were different in patients compared to controls (p < 0.05). In addition, we found some suggestive metabolites (without enough predictability) by multivariate analysis (VIP scores > 2), such as lipoproteins, lactate, glucose, unsaturated lipids, isoleucine, and proline, that might be relevant to the process of pharmacoresistance in the comparison between patients with refractory and responsive MTLE. The identified metabolites for the comparison between MTLE patients and controls were linked to different biological pathways related to cell-energy metabolism and pathways related to inflammatory processes and the modulation of neurotransmitter release and activity in MTLE. In conclusion, in addition to insights into the mechanisms underlying MTLE, our results suggest that plasma metabolites may be used as disease biomarkers. These findings warrant further studies exploring the clinical use of metabolites to assist in decision-making when treating patients with MTLE. [ABSTRACT FROM AUTHOR]

ANCA vasculitis, caused by antibodies named ANCA (anti-neutrophilic cytoplasmic autoantibodies), is an autoimmune disorder affecting small blood vessels of the body. Among p-ANCA and c-ANCA, c-ANCA (cytoplasmic ANCA) usually targets proteinase three inside neutrophils, causing inflammation of blood vessels. Herein, we report a case of a 56-year-old female patient with c-ANCA-associated vasculitis. The patient presented with a localized skin thickening on the medial aspect of the left thigh and an oral ulcer. Skin biopsy shows erythema induratum (nodular vasculitis). After several investigations, we found c-ANCA positive and concluded the diagnosis as c-ANCA-associated vasculitis. We treat the patient with injectable methylprednisolone, injectable cyclophosphamide, and Mesna. Then we gave oral mycophenolate mofetil and prednisolone. [ABSTRACT FROM AUTHOR]

Ribonucleotide Reductase (RNR) is a two-subunit (RRM1, RRM2) enzyme, responsible for the conversion of ribonucleotides to deoxyribonucleotides required for DNA replication. To evaluate RNR as a biomarker of response to 5-azacytidine, we measured RNR mRNA levels by a quantitative real-time PCR in bone marrow samples of 98 patients with myelodysplastic syndrome (MDS) treated with 5-azacytidine with parallel quantification of the gene promoter's methylation. Patients with low RRM1 levels had a high RRM1 methylation status (p = 0.005) and a better response to treatment with 5-azacytidine (p = 0.019). A next-generation sequencing for genes of interest in MDS was also carried out in a subset of 61 samples. Splicing factor mutations were correlated with lower RRM1 mRNA levels (p = 0.044). Our results suggest that the expression of RNR is correlated with clinical outcomes, thus its expression could be used as a prognostic factor for response to 5-azacytidine and a possible therapeutic target in MDS. [ABSTRACT FROM AUTHOR]

Abstract Background: The 4T1 is a mice transplantable mammary carcinoma cell line with the highly tumorigenic and invasive specification, making it suitable preclinical oncology model for triple- negative breast cancer (TNBC). The aim of this pilot study was to model the clinical stages and evaluate the response to treatment with the paclitaxel (PTX) and doxorubicin (DOX) in tumors caused by this cell line. Methods: The syngeneic tumors were developed in BALB/c female mice by 4T1 cell line. The mice were randomly distributed into three different groups, each contains four. A group of four was considered as healthy normal. Following tumor growth reached 100-300 mm3, two groups were received the maximum tolerated dose (MTD) of paclitaxel and doxorubicin, respectively. The group of sham control was injected with normal saline. The tumors and the tumor margins tissues were removed by surgery one week following chemotherapy. Angiogenesis genes and MVD were analyzed by real-time PCR and immunohistochemistry, respectively. Response to treatment was also assessed by standard methods of H&E staining. Results: TNBC tumors were confirmed by pathological staining. The volume of tumors and the angiogenesis gene expressions of VEGFR1, VEGFR2, and HIF1α were decreased in treated-tumors compared to control with p

Background: Heat shock proteins (Hsp) are chaperones playing essential roles in skeletal muscle physiology, adaptation to exercise or stress, and activation of inflammatory cells. We aimed to assess Hsp90 in patients with idiopathic inflammatory myopathies (IIM) and its association with IIM-related features. Methods: Hsp90 plasma levels were analyzed in a cross-sectional cohort (277 IIM patients and 157 healthy controls [HC]) and two longitudinal cohorts to assess the effect of standard-of-care pharmacotherapy (n=39 in early disease and n=23 in established disease). Hsp90 and selected cytokines/chemokines were measured by commercially available ELISA and human Cytokine 27-plex Assay. Results: Hsp90 plasma levels were increased in IIM patients compared to HC (median [IQR]: 20.2 [14.3–40.1] vs 9.8 [7.5–13.8] ng/mL, p<0.0001). Elevated Hsp90 was found in IIM patients with pulmonary, cardiac, esophageal, and skeletal muscle involvement, with higher disease activity or damage, and with elevated muscle enzymes and crucial cytokines/chemokines involved in the pathogenesis of myositis (p<0.05 for all). Plasma Hsp90 decreased upon pharmacological treatment in both patients with early and established disease. Notably, Hsp90 plasma levels were slightly superior to traditional biomarkers, such as C-reactive protein and creatine kinase, in differentiating IIM from HC, and IIM patients with cardiac involvement and interstitial lung disease from those without these manifestations. Conclusions: Hsp90 is increased systemically in patients with IIM. Plasma Hsp90 could become an attractive soluble biomarker of disease activity and damage and a potential predictor of treatment response in IIM. [ABSTRACT FROM AUTHOR]

Introduction and objectives: Little is known about primary biliary cholangitis (PBC) in non-whites. The purpose of this study was to evaluate clinical features and outcomes of PBC in a highly admixed population. Material and methods: The Brazilian Cholestasis Study Group multicentre database was reviewed to assess demographics, clinical features and treatment outcomes of Brazilian patients with PBC. Results: 562 patients (95% females, mean age 51 § 11 years) with PBC were included. Concurrent autoimmune diseases and overlap with autoimmune hepatitis (AIH) occurred, respectively, in 18.9% and 14%. After a mean follow-up was 6.2 § 5.3 years, 32% had cirrhosis, 7% underwent liver transplantation and 3% died of liver-related causes. 96% were treated with ursodeoxycholic acid (UDCA) and 12% required add-on therapy with fibrates, either bezafibrate, fenofibrate or ciprofibrate. Response to UDCA and to UDCA/fibrates therapy varied from 39%-67% and 42-61%, respectively, according to different validated criteria. Advanced histological stages and non-adherence to treatment were associated with primary non-response to UDCA, while lower baseline alkaline phosphatase (ALP) and aspartate aminotransferase (AST) levels correlated with better responses to both UDCA and UDCA/fibrates. Conclusions: Clinical features of PBC in highly admixed Brazilians were similar to those reported in Caucasians and Asians, but with inferior rates of overlap syndrome with AIH. Response to UDCA was lower than expected and inversely associated with histological stage and baseline AST and ALP levels. Most of patients benefited from add-on fibrates, including ciprofibrate. A huge heterogeneity in response to UDCA therapy according to available international criteria was observed and reinforces the need of global standardization. [ABSTRACT FROM AUTHOR]

Background: Obesity has been associated with increased incidence of myelodysplastic syndromes (MDS). Recently intriguing data in mouse models suggested that obesity increases survival in animals with MDS. Methods: This was a retrospective analysis using the Moffitt MDS database. Obesity was defined by using body mass index (BMI), whereby a BMI ≥ 30 was regarded as obese. Results: Among 3089 MDS patients with known BMI, 963 patients (31%) were categorized as obese. There were no differences in baseline characteristics between patients with BMI ≥ 30 and those with <30. The median OS for patients with BMI ≥ 30 was 34 months compared to 37 months for those with BMI < 30 (p 0.04). For patients with lower-risk MDS median OS was 52 months versus 57 months, respectively, (p 0.08) while for higher-risk patients median OS was 17 months for both groups. The rate of AML transformation was 36% for patients with BMI ≥ 30 compared to 32% for those with BMI < 30 (p 0.009). There was no difference in response to azacitidine. In multivariable analysis, BMI was associated with inferior OS. For patients < 45 years old, the median OS was 25 months for patients with BMI ≥ 30 compared to 116 months for those with BMI < 30 (p 0.034). Conclusions: Obesity is associated with inferior overall survival (OS) in MDS patients in less than 65 years old and lower MDS risk. Impact of obesity on the outcome of MDS is being explored in both mice and human. Here we reported the impact of obesity on OS in MDS patients. Obesity is associated with inferior OS in MDS patients particularly younger age groups and lower MDS risk. [ABSTRACT FROM AUTHOR]

reducing production and death. The disease in endemic areas would be mild or subclinical in indigenous cattle and clinically acute in exotics. OBJECTIVES: This study was conducted to evaluate the resistance of indigenous cattle in comparison with Holstein and crossbred cattle against Theileria annulata through assessment of clinical signs and response to treatment. METHODS: For this purpose, the data history and clinical examination were observed on 51 naturally affected cattle with T. annulata (17 Holstein, 17 crossbred and 17 indigenous cows). Examination of blood smears was used for diagnosis. Detection of schizonts in lymph node punctured smears confirmed validity of the suspect samples. All three groups of cows were treated with buparvaquone along with oxytetracycline. Their clinical signs and the results of blood smear examinations were recorded before and 48 hours after treatment. The severity of clinical signs, parasitemia rates and response to treatment were compared among the groups. RESULTS: The results showed significant difference (p

Introduction and objectives: Little is known about primary biliary cholangitis (PBC) in non-whites. The purpose of this study was to evaluate clinical features and outcomes of PBC in a highly admixed population. Material and methods: The Brazilian Cholestasis Study Group multicentre database was reviewed to assess demographics, clinical features and treatment outcomes of Brazilian patients with PBC. Results: 562 patients (95% females, mean age 51 ± 11 years) with PBC were included. Concurrent autoimmune diseases and overlap with autoimmune hepatitis (AIH) occurred, respectively, in 18.9% and 14%. After a mean follow-up was 6.2 ± 5.3 years, 32% had cirrhosis, 7% underwent liver transplantation and 3% died of liver-related causes. 96% were treated with ursodeoxycholic acid (UDCA) and 12% required add-on therapy with fibrates, either bezafibrate, fenofibrate or ciprofibrate. Response to UDCA and to UDCA/fibrates therapy varied from 39%-67% and 42-61%, respectively, according to different validated criteria. Advanced histological stages and non-adherence to treatment were associated with primary non-response to UDCA, while lower baseline alkaline phosphatase (ALP) and aspartate aminotransferase (AST) levels correlated with better responses to both UDCA and UDCA/fibrates.Conclusions: Clinical features of PBC in highly admixed Brazilians were similar to those reported in Caucasians and Asians, but with inferior rates of overlap syndrome with AIH. Response to UDCA was lower than expected and inversely associated with histological stage and baseline AST and ALP levels. Most of patients benefited from add-on fibrates, including ciprofibrate. A huge heterogeneity in response to UDCA therapy according to available international criteria was observed and reinforces the need of global standardization.

BackgroundHeat shock proteins (Hsp) are chaperones playing essential roles in skeletal muscle physiology, adaptation to exercise or stress, and activation of inflammatory cells. We aimed to assess Hsp90 in patients with idiopathic inflammatory myopathies (IIM) and its association with IIM-related features.MethodsHsp90 plasma levels were analyzed in a cross-sectional cohort (277 IIM patients and 157 healthy controls [HC]) and two longitudinal cohorts to assess the effect of standard-of-care pharmacotherapy (n=39 in early disease and n=23 in established disease). Hsp90 and selected cytokines/chemokines were measured by commercially available ELISA and human Cytokine 27-plex Assay.ResultsHsp90 plasma levels were increased in IIM patients compared to HC (median [IQR]: 20.2 [14.3–40.1] vs 9.8 [7.5–13.8] ng/mL, p

Introduction: Anal squamous cell carcinoma (ASC) is a rare gastrointestinal malignancy showing an increased incidence over the past decades. YKL-40 is an immune modulator and pro-angiogenetic factor that showed a promising prognostic and predictive potential in several malignancies, but limited data are available for ASC. This study aims to provide an extensive evaluation of the prognostic and predictive role of YKL-40 in a multicenter cohort of ASC patients., Methods: We retrospectively retrieved 72 consecutive cases of ASC diagnosed between February 2011 and March 2021. Both serum and tissue protein expression of YKL-40 were assessed, the latter in ASC tumor cells and peritumor immune cells., Results: Increased YKL-40 serum levels at the time of diagnosis were associated with older age ( p  = 0.035), presence of cardiovascular/metabolic comorbidities ( p  = 0.007), and death for any cause ( p  = 0.011). In addition, high serum levels of YKL-40 were associated with a poor prognosis (HR: 2.82, 95% CI: 1.01-7.84; p  = 0.047). Protein expression of YKL-40 in ASC tumor cells was significantly associated with low tumor grade ( p  = 0.031), while the increased expression in peritumor immune cells was associated with a worse response of patients to chemoradiotherapy ( p  = 0.007). However, YKL-40 protein expression in ASC tumor cells or peritumor immune cells did not significantly impact patient overall survival., Discussion: In conclusion, YKL-40 resulted a relevant prognostic (serum level) and predictive (tissue protein expression in peritumor immune cells) biomarker and can considerably improve ASC patient clinical management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gambella, Senetta, Falco, Ricci, Mangherini, Tampieri, Fissore, Orlando, Manetta, Mengozzi, Mistrangelo, Bertero and Cassoni.)

Objective: Pembrolizumab and bevacizumab both have antitumor activity. According to NCCN updated guideline the benefit of pembrolizumab or bevacizumab as a first line in management of advanced nonsmall cell lung cancer (NSCLC) is documented in randomized controlled studies. The study aimed to evaluate the response and complications of patients with advanced NSCLC treated with pembrolizumab or bevacizumab plus chemotherapy. Methods: This study was a retrospective cohort study of patients with advanced nonsquamous NSCLC who received cisplatin with pemetrexed combined with pembrolizumab (A group) or bevacizumab (B group) from 07/02/2018 to 07/03/2021 at Peking University Cancer Hospital. Progression-free survival (PFS) was the primary outcome. The secondary outcomes included overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), and adverse events (AEs). Results: This study included 66 patients, 34 in A group and 32 in B group. There were no differences in median PFS (7.6 vs 9.9 months, P =.601). There were no differences in median OS (23.1 vs 24.2 months, P =.782). There were no differences in ORR (57.6 % vs 41.9 %, P =.211) and DCR (93.9 % vs 100.0 %, P =.164) between 2 groups. The occurrence of AEs was similar. No new safety signals were observed. Grade 3 to 4 treatment-related AEs occurred in 17 (50.0 %) patients of A group and in 12 (37.5 %) of B group (P >.05). Conclusion: The addition of pembrolizumab or bevacizumab to pemetrexed plus cisplatin was well tolerated and resulted in a clinically meaningful treatment benefit in advanced nonsquamous NSCLC. When pembrolizumab is not suitable, bevacizumab plus chemotherapy may be an option. [ABSTRACT FROM AUTHOR]

Both specific and innate immune responses play important roles in autoimmune encephalitis (AE). We aimed to explore the predictive value of the systemic inflammation index (SII) at admission as a peripheral biomarker of treatment response of AE. A total of 146 patients diagnosed with AE in the First Affiliated Hospital of Zhengzhou University from January 1, 2018 to September 22, 2020 were retrospectively and consecutively analyzed as per the inclusion criteria and divided into two groups according to their response to immunotherapy after 30 days. The predictive value of the SII as a peripheral biomarker for AE treatment response was calculated using the receiver operating characteristic curve analysis, which showed that the best SII cut-off value for predicting poor response to AE treatment was 863.3; the area under the curve was 0.75, with 83.0% sensitivity and 72.0% specificity. The risk factors for poor response to AE treatment were analyzed; univariable analysis showed that the rate of decreased level of consciousness, rate of cognitive or mental behavior abnormality, cerebrospinal fluid pressure, blood neutrophils, platelets, time until treatment initiation, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and SII were significantly higher in patients with poor response to AE immunotherapy after 30 days than in patients with good response. Meanwhile, the blood lymphocyte counts and Glasgow Coma Scale (GCS) scores in patients with poor response were significantly lower than those in patients with good response (all p < 0.05), and multivariable binary logistic regression with backward stepwise method showed that decreased levels of consciousness, time until treatment initiation and SII were associated with poor response to immunotherapy. Moreover, the SII ≤ 863.3 group had lower rates of decreased consciousness levels, admission to the intensive care unit, and mechanical ventilation; lower cerebrospinal fluid pressure, blood neutrophil count, and platelet count; and higher blood lymphocyte count and GCS scores. The SII was associated with worsened disease severity and poor response to treatment after 30 days of the initially diagnosed AE, and patients with an SII > 863.3 were more likely to have poor response to immunotherapy. [ABSTRACT FROM AUTHOR]

Featured Application: Radiomics may be a useful non-invasive biomarker in the assessment of response to perioperative chemotherapy in gastric cancer patients. Perioperative chemotherapy (p-ChT) with a fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) scheme is the gold standard of care for locally advanced gastric cancer. We aimed to test CT radiomics performance in early response prediction for p-ChT. Patients with advanced gastric cancer who underwent contrast enhanced CT prior to and post p-ChT were retrospectively enrolled. Histologic evaluation of resected specimens was used as the reference standard, and patients were divided into responders (TRG 1a-1b) and non-responders (TRG 2-3) according to their Becker tumor regression grade (TRG). A volumetric region of interest including the whole tumor tissue was drawn from a CT portal-venous phase before and after p-ChT; 120 radiomic features, both first and second order, were extracted. CT radiomics performances were derived from baseline CT radiomics alone and ΔRadiomics to predict response to p-ChT according to the TRG and tested using a receiver operating characteristic (ROC) curve. The final population comprised 15 patients, 6 (40%) responders and 9 (60%) non-responders. Among pre-treatment CT radiomics parameters, Shape, GLCM, First order, and NGTDM features showed a significant ability to discriminate between responders and non-responders (p < 0.011), with Cluster Shade and Autocorrelation (GLCM features) having AUC = 0.907. ΔRadiomics showed significant differences for Shape, GLRLM, GLSZM, and NGTDM features (p < 0.007). MeshVolume (Shape feature) and LongRunEmphasis (GLRLM feature) had AUC = 0.889. In conclusion, CT radiomics may represent an important supportive approach for the radiologic evaluation of advanced gastric cancer patients. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF)-like chronic disease progression despite treatment cannot be predicted with confidence in interstitial lung diseases (ILDs) other than IPF at the time of diagnosis. We review key determinants of a progressive fibrotic phenotype, at initial diagnosis of an ILD other than IPF. Medline literature searches (2000 to 2020) were undertaken with regard to the issues discussed in this review. The definition of the progressive fibrotic phenotype in non-IPF patients should remain real world, with a conclusion reached by an experienced clinician that progression has occurred despite the use of appropriate historical therapies, on a case by case basis. There is an urgent need for pathogenetic studies to identify pathways and genetic predilections that are common to chronic progressive fibrosis across different diseases. Efforts should also be focused on the identification of the progressive fibrotic phenotype at first presentation, potentially through a combination of CT and biopsy evaluation and the definition of a biomarker profile associated with subsequent disease progression. Recent anti-fibrotic trials of non-IPF disorders should lead to trials of combination regimens of anti-fibrotic agents and immunomodulatory or other therapies specific to individual diseases. [ABSTRACT FROM AUTHOR]

Cytokines seem to play a crucial role in physiological and pathological conditions of acute myeloid leukemia (AML). The aim of this study was to evaluate the expression levels of interleukins-6 (IL-6) and IL-18 in patients with AML and its correlation with response to therapy and graft versus host disease (GvHD) after bone marrow transplantation. The expression levels of IL-6 and IL-18 genes were done in all patients and compared with matched control. Complete remission (CR) was used for evaluation of the effects of these cytokines on response to treatment in patients group. The expression level of these cytokines was also evaluated in patients who underwent bone marrow transplantation and experienced acute GvHD in compare with patients without aGvHD. Il-6 gene expression level was significantly higher in these patients in comparison with control but Il-18 gene expression level was not statistically significant compared to control group. Il-6 and also Il-18 expression levels were significantly higher in patients without a response to treatment according to CR compared to patient's whit response to treatment as well as patients experienced aGvHD after bone marrow transplantation. IL-6 and Il-18 are important markers in the progression of the disease and could be considered as a prognostic marker in acute leukemia. It is recommended that more studies with larger study groups and more involved cytokines are needed for more evaluation of the cytokine roles in pathophysiology and progression of acute leukemia. [ABSTRACT FROM AUTHOR]

Background & aimsLittle is known about how weight loss affects magnetic resonance imaging (MRI) of liver fat and volume or liver histology in patients with nonalcoholic steatohepatitis (NASH). We measured changes in liver fat and liver volume associated with weight loss by using an advanced MRI method.MethodsWe analyzed data collected from a previous randomized controlled trial in which 43 adult patients with biopsy-proven NASH underwent clinical evaluation, biochemical tests, and MRI and liver biopsy analyses at the start of the study and after 24 weeks. We compared data between patients who did and did not have at least 5% decrease in body mass index (BMI) during the study period.ResultsTen of 43 patients had at least a 5% decrease in BMI during the study period. These patients had a significant decrease in liver fat, which was based on MRI proton density fat fraction estimates (18.3% ± 7.6% to 13.6% ± 13.6%, P = .03), a relative 25.5% reduction. They also had a significant decrease in liver volume (5.3%). However, no significant changes in levels of alanine aminotransferase or aspartate aminotransferase were observed with weight loss. Thirty-three patients without at least 5% decrease in BMI had insignificant increases in estimated liver fat fraction and liver volume.ConclusionsA reduction in BMI of at least 5% is associated with significant decrease in liver fat and volume in patients with biopsy-proven NASH. These data should be considered in assessing effect size in studies of patients with nonalcoholic fatty liver disease or obesity that use MRI-estimated liver fat and volume as end points.

Both specific and innate immune responses play important roles in autoimmune encephalitis (AE). We aimed to explore the predictive value of the systemic inflammation index (SII) at admission as a peripheral biomarker of treatment response of AE. A total of 146 patients diagnosed with AE in the First Affiliated Hospital of Zhengzhou University from January 1, 2018 to September 22, 2020 were retrospectively and consecutively analyzed as per the inclusion criteria and divided into two groups according to their response to immunotherapy after 30 days. The predictive value of the SII as a peripheral biomarker for AE treatment response was calculated using the receiver operating characteristic curve analysis, which showed that the best SII cut-off value for predicting poor response to AE treatment was 863.3; the area under the curve was 0.75, with 83.0% sensitivity and 72.0% specificity. The risk factors for poor response to AE treatment were analyzed; univariable analysis showed that the rate of decreased level of consciousness, rate of cognitive or mental behavior abnormality, cerebrospinal fluid pressure, blood neutrophils, platelets, time until treatment initiation, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and SII were significantly higher in patients with poor response to AE immunotherapy after 30 days than in patients with good response. Meanwhile, the blood lymphocyte counts and Glasgow Coma Scale (GCS) scores in patients with poor response were significantly lower than those in patients with good response (all p < 0.05), and multivariable binary logistic regression with backward stepwise method showed that decreased levels of consciousness, time until treatment initiation and SII were associated with poor response to immunotherapy. Moreover, the SII ≤ 863.3 group had lower rates of decreased consciousness levels, admission to the intensive care unit, and mechanical ventilation; lower cerebrospinal fluid pressure, blood neutrophil count, and platelet count; and higher blood lymphocyte count and GCS scores. The SII was associated with worsened disease severity and poor response to treatment after 30 days of the initially diagnosed AE, and patients with an SII > 863.3 were more likely to have poor response to immunotherapy.

Objective This study evaluated anti-modified citrullinated vimentin (anti-MCV) performance in determining the clinical picture and outcomes of palindromic rheumatism (PR). Methods In a retrospective study, patients with PR with at least 1 year of follow-up diagnosed according to clinical criteria were enrolled. Anti-MCV antibodies were measured, and levels >20 IU/mL were considered positive. Disease prognosis was assessed according to patients acquiring remission and preventing PR from developing into rheumatoid arthritis (RA) or other diseases. Results Seventy-six patients with PR with a mean follow-up of 30.57 months (median = 21 months; minimum = 12 months; maximum = 48 months) were included in the study. Anti-MCV antibodies were positive in 69.7% of patients. Metacarpophalangeal (MCP) joint involvement and positive anti-cyclic citrullinated peptides were significantly higher in patients who were anti-MCV-positive, whereas ankle joint involvement was significantly lower. No significant correlation was observed between the anti-MCV titer and the severity of attacks. Remission in patients who were anti-MCV-positive and negative was 75.5% and 78.3%, respectively, with no significant difference. Evolution to RA was observed in only 3.8% of patients who were anti-MCV-positive. No patients who were anti-MCV-negative developed RA. Conclusion Except for MCP and ankle joint involvement, anti-MCV was not helpful in determining the clinical picture and outcome of PR. [ABSTRACT FROM AUTHOR]